DESCRIPTION (adapted from the applicantion's abstract): Since its inception in 1987, the University of Cincinnati (UC) ACTU has made contributions to the overall mission of the ACTG in a number of key areas. The UC ACTU has provided both scientific and administrative leadership especially in opportunistic infections, and more recently, in antiretroviral studies, HIV- associated neurologic diseases, research nursing, and study design. In the current cycle, the UC ACTU proposes to continue to perform a broad range of clinical trials and substudies to assure maximum UC ACTU contribution to the objectives of the ACTG research agenda. These include to translate the findings of basic research conducted at UC on immunopathogenesis of Pneumocystis carinii and other opportunistic pathogens that may help determine when and if prophylaxis can be discontinued safely in antiretroviral therapy responders. Also, to explore microbial and immunologic measures which define risk for the protection against Pneumocystis as a basis for adjunctive immune- based therapy and prophylaxis. In addition to study the pathogenesis and clinical significance of hepatitis C/HIV co-infection in the HARRT era, and use this knowledge to develop improved treatments. Another Aim is to continue to elucidate the underlying mechanisms in the neuropathogenesis of HIV infection, and exploit these mechanisms in the development of new therapeutic modalities for central nervous system HIV infection, including HIV dementia and multifocal leukoencephalopathy. The UC ACTU will also work to develop treatment strategies for the management of patients with discordant responses to current antiretroviral therapy and to develop simplified, potent treatment strategies, including the use of novel agents, to enhance antiretroviral adherence and therefore improve clinical outcome. The short and longer-term incremental cost of quality-adjusted life expectancy associated with various treatment strategies using utility assessment will also be studied. Finally, the UC ACTU proposes to evaluate whether an intensive educational intervention that is paced by the patient yields improved short and long-term virologic suppression in naive patients.